Systemic lupus erythematosus (SLE) is severe disease characterized by chronic inflammation (swelling, redness, and pain). Patients having this disease produce antibodies that target cells of their own body tissues. The antibody-targeted cells are then destroyed by white blood cells in the body causing cell death that leads to inflammation. As such, SLE is known as an autoimmune disease. Crow et al., “Etiologic Hypothesis for Systemic Lupus Erythematosus,” in LaHita, Systemic Lupus Erythematosus, Churchill, Livingston, N.Y. (1987) page 51 ff. SLE affects many body systems including skin, joints, blood, lungs, kidneys, heart, brain, gastrointestinal tract, bone marrow, liver, and nervous tract. Crow et al., “Etiologic Hypothesis for Systemic Lupus Erythematosus,” in LaHita, Systemic Lupus Erythematosus, Churchill, Livingston, N.Y. (1987) page 51 ff.
The present diagnosis for SLE is an art form practiced by rheumatologists or other physicians. In one form, the practitioner seeks eleven indicia: malar rash, discoid rash, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, hematologist disorder, immunologic disorder and anti-nuclear antibodies (ANA). SLE is presumed if four of the eleven are present. LaHita, Lupus Erythematosus, 2nd. ed., Churchill, Livingston, N.Y. (1992) pages 372-373. Other assays that can be and are used to diagnose the presence of SLE in a patient include separate assays for ANA, complement levels, the presence of rheumatoid factor, hyperglobulinemia, false positive syphilis test, LE cell test, anti-DNA antibodies, anti-SMP antibodies, anti-RMP antibodies, anti-Smith antibodies, anemia, leucopenia, thrombocytopenia, positive direct Coombs' test, and anti-double-stranded DNA (anti-dsDNA) antibodies. LaHita, Lupus Erythematosus, 2nd. ed., Churchill, Livingston, N.Y. (1992). As is seen, none of these assays is definitive for the disease.
Although there is marked similarity to an infectious entity, an exhaustive search for an etiologic agent has not until recently yielded any candidates that fulfill the criteria for causation of this disease until now. Crow et al., “Etiologic Hypothesis for Systemic Lupus Erythematosus,” in Lahita Systemic Lupus Erythematosus, Churchill, Livingston, N.Y. (1987) page 51 ff; Pincus, Arthr. & Rheum., 20:149-158 (1982). More recently, the consideration of bacteria and mycoplasmas with unique capacities to perturb immune systems has led to new hypotheses in regard to the infectious trigger of SLE.
For example, intra-erythrocyte organisms with characteristics that were thought to be Haemobartonella-like were first suggested as exogenous agents in SLE by Kallick et al., Nature New Biology, 236:145-146 (1972). That report was further developed by a later report of antigenic similarities between SLE or lupus nephritis and diseases caused by Anaplasma marginale, an intra-erythrocytic parasite of cattle, and a member of the family Anaplasmataceae. Kallick et al., Arthr. Rheum., 23:197-205 (1980).
Further, exogenous intra-erythrocytic structures seen in the same erythrocyte by Giemsa or acridine orange staining and phase contrast microscopy have been observed in most patients with SLE, and are illustrated in U.S. Pat. Nos. 5,972,309 and 5,795,563. These stained structures are identical or similar in appearance to Mycoplasma haemofelis, the causative agent of feline infectious anemia, as discussed below.
A specific group of Mycoplasmas recognized as Haemoplasmas also produce hematological disease in cats, dogs, mice, and swine. They exhibit latency and chronicity as well as an acute syndrome and intermittent infection of the erythrocytes and can be seen in the acute phase of early infection, although not easily in the chronic phase. They have not been reproducibly cultured or transmitted to other than related animal species.
The locus of infection of the erythrocyte in the Haemoplasmas, M. haemocanis, M. haemofelis, and M. haemosuis is seen on the surface of the erythrocytes, though in mice, M. haemomuris also known as Haemobartonella muris, is within the erythrocyte. Early descriptions of these agents were mediated by the observed position of the parasite on the erythrocyte.
In animal disease, antibiotics control hemolytic anemia, the primary pathologic event, only if given early in the course of the illness. Late in the course of animal illness, the hemolytic anemia is mediated by antibody formation and antibiotics do not appear to affect the course. In veterinary literature, one antibiotic that appears to suppress some of the clinical manifestations is tetracycline and analogues. Franklin et al., Southwestern Vet., 15:131-139 (1962).
Several humans with SLE or connective tissue disease have been treated with tetracycline (doxycycline) in preliminary work of the inventor based on the presumption of Anaplasmataceae parasitemia. Wanduragala et al. in, Rickettsial and Chlamydial Diseases of Domestic Animals, Waldehewit ed., Pergamon Press, Oxford, (1993) page 79.
Aureomycin, a tetracycline-like drug, had been proposed as a treatment in the 1940s for rheumatoid diseases with claims of some degree of success. [Brown et al., J. Lab. Clin. Med., 34:1404-1410 (1949); Scheff et al., Infec. Dis., 98:113 (1956).] These phenomena suggest that the tetracycline drugs are of benefit in the syndrome of SLE.
Current SLE therapy relies upon heavy steroid use concurrent with immunosuppressives and/or plasmaphoresis. It is of interest that infections in animals by bacteria then called Anaplasmataceae, are almost uniquely among infectious diseases, ameliorated by steroids. [Scheff et al., Infec. Dis., 98:113 (1956); Ristic et al., J. Vet. Res., 19:37 (1958)]
No presently used therapy is completely satisfactory. Although the life expectancy of lupus patients has been considerably increased, the ravages of therapeutic side effects and the constant fatigue take a severe toll. Dubois, Lupus Erythematosus, 2d ed., U.S. California Press, Los Angeles (1974).
It would therefore be beneficial if a more definitive diagnosis of SLE patients could be found, and if the patients so identified could be more effectively treated. The description that follows describes a diagnostic method that is believed to be definitive for SLE, and a treatment regimen that deals with the causative agent in SLE and can eliminate that agent from a patient's body.